Dimethyl Sulfoxide → HCID 10995440, compound

HRID 963277Notes

Reaction equation

HRID 963277 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([O:14][C:15]([N:17]1[C@@H:30]([C:31]#[C:32]/[CH:33]=[CH:34]\[C:35]#[CH:36])[C@:29]23[O:37][C@:24]2([C@@H:25]([OH:43])[C:26]([O:41][CH3:42])([O:39][CH3:40])[CH2:27][C@@H:28]3[CH3:38])[C:23]2[CH:22]=[C:21]([O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH:20]=[CH:19][C:18]1=2)=[O:16])[CH:12]=[CH2:13].C(N(CC)CC)C.P([O-])([O-])([O-])=O>ClCCl>[CH2:11]([O:14][C:15]([N:17]1[C@@H:30]([C:31]#[C:32]/[CH:33]=[CH:34]\[C:35]#[CH:36])[C@:29]23[O:37][C@:24]2([C:25](=[O:43])[C:26]([O:39][CH3:40])([O:41][CH3:42])[CH2:27][C@@H:28]3[CH3:38])[C:23]2[CH:22]=[C:21]([O:44][Si:45]([C:48]([CH3:49])([CH3:51])[CH3:50])([CH3:46])[CH3:47])[CH:20]=[CH:19][C:18]1=2)=[O:16])[CH:12]=[CH2:13]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 1061PhosphateHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 86752753HCID 86752753, compound

Product 1

HCID 10995440HCID 10995440, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Dimethyl sulfoxide (4.22 mL, 59.5 mmol, 15.0 equiv) was added to a solution of oxalyl chloride (3.46 mL, 39.7 mmol, 10.0 equiv) in dichloromethane (75 mL) at -78° C. After stirring at -78° C. for 20 min, a solution of allyl(6S,6aS,7S,10R,10aS)-2-(tert-butyldimethylsiloxy)-6-[(Z)-3-hexene-1,5-diynyl]-7,8,9,10-tetrahydro-10-hydroxy-9,9-dimethoxy-7-methyl-6a,10a-epoxyphenanthridine-5(6H)-carboxylate (23, 2.30 g, 3.97 mmol, 1 equiv) in dichloromethane (75 mL) was added over 10 min via cannula to the cold reaction solution. The reaction mixture was warmed to -40° C. and was held at that temperature for 10 h. The reaction mixture was then cooled to -78° C., triethylamine (16.6 mL, 119 mmol, 30.0 equiv) was added, and the resulting solution was stirred in an ice bath for 30 min. The product solution was poured into aqueous phosphate buffer solution (pH 7, 0.05M in sodium hydrogen phosphate and 0.05M in potassium dihydrogen phosphate, 150 mL). The aqueous layer was separated and extracted further with dichloromethane (2×150 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was purified by flash column chromatography (2% ethyl acetate-dichloromethane initially, grading to 5% ethyl acetate-dichloromethane) to afford allyl(6S,6aS,7S,10aR)-2-(tert-butyldimethylsiloxy)-6-[(Z)-3-hexene-1,5-diynyl]-7,8,9,10-tetrahydro-9,9-dimethoxy-7-methyl-10-oxo-6a,10a-epoxyphenanthridine-5(6H)-carboxylate (24) as a light brown foam (2.10 g, 92%). ##STR35##

Workup

  1. temperatureThe reaction mixture was warmed to -40° C.
  2. waitwas held at that temperature for 10 h
  3. temperatureThe reaction mixture was then cooled to -78° C.
  4. stirringthe resulting solution was stirred in an ice bath for 30 min
  5. customThe aqueous layer was separated
  6. extractionextracted further with dichloromethane (2×150 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationwere concentrated
  9. customThe residue was purified by flash column chromatography (2% ethyl acetate-dichloromethane initially

Sources & evidence

ORD record
ord-63283c92aa8d438faad35f16e67ff19d
Source dataset
uspto-grants-1998_06
Patent number
US05763451

Reaction notes

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